Search

Introduction: The pursuit of Equity, Diversity and Inclusion (EDI) in healthcare education has garnered significant attention in recent years, reflecting a broader societal imperative for equitable healthcare delivery. However, existing curricula within geriatric healthcare education may not adequately address these diverse needs within their educational frameworks, inadvertently resulting in disparities in care delivery and outcomes. Within the realm of geriatric healthcare, addressing EDI is particularly crucial due to the diverse needs of older adult populations and the imperative for healthcare professionals to deliver culturally humble care. This review provides a comprehensive overview of strategies and curricular strategies, actions and/or initiatives to promote EDI within geriatric healthcare professional education., Methods: This paper presents a protocol for a forthcoming scoping review. The methodology for this scoping review adheres to the framework outlined in the Joanna Briggs Institute (JBI) Manual, encompassing four main stages: (1) formulation of a search strategy, (2) screening and selection of evidence, (3) data extraction, and (4) analysis. We will conduct a comprehensive search of peer-reviewed and empirical literature. Additionally, we will explore the reference lists of included studies to identify any relevant sources. The synthesis of findings will be conducted through a narrative approach. Reporting of the methods and results will adhere to the guidelines provided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)., Discussion: Healthcare professionals must possess the knowledge, skills, and attitudes necessary to deliver culturally humble care that respects and responds to diverse older adults' unique needs and preferences. The review aims to fill a crucial gap in the literature by providing a comprehensive overview of strategies and curricular interventions designed to promote EDI within geriatric healthcare professional education. By mapping these strategies, actions and/or initiatives, the review seeks to identify trends, challenges, and opportunities for advancing EDI within geriatric care. The forthcoming review serves as a call to action for educators, healthcare institutions, and decision makers to prioritize EDI within geriatric healthcare education. The review identifies effective strategies and interventions for promoting EDI, providing actionable insights to inform the development of inclusive curricula, training programs, and institutional policies, which can contribute to cultivating a healthcare workforce better equipped to address the complex and evolving needs of aging populations equitably and compassionately., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kokorelias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Currently, literature on spiritual health remains limited. Even more so, literature on spiritual health remains limited in Canada. This is exacerbated by the fact that spiritual health is a term that remains widely contested with no concrete definition. Meanwhile, the semantic connection between "religion" and "spirituality" remains ambiguous in the West and scholars hold different positions. In this paper, we outline our scoping review protocol to describe the current landscape of spiritual health and spirituality (in relation to health) research in Canada, including the meaning and understanding behind these two concepts., Methods and Analysis: This protocol for our scoping review is documented in accordance with the PRISMA-P reporting guidelines and adheres to Arksey and O'Malley's scoping review methodology. We will conduct a search strategy across select electronic databases and review the reference lists of chosen papers. Two reviewers, HMB and MM, will independently and blindly screen all title/abstracts and full-text studies for eligibility. Any Canadian-situated studies that centrally mention and focus on "spirituality" or "spiritual health" will be included. Relevant variables will be extracted through an iterative process, with the data charting being continuously reviewed and refined. Findings from this scoping review will support the future of health research and conceptual expansion of health beyond the mental, physical and social. Approval from a research ethics board is not required, nor has it been obtained, as the data is derived from journal articles and academic publications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boutros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Due to structural marginalization, sex workers experience health inequities including a high prevalence of sexually transmitted and blood-borne infections, mental health disorders, trauma, and substance use, alongside a multitude of barriers to HIV and substance use services. Given limited evidence on sex workers' broader primary healthcare access, we aimed to examine structural factors associated with primary care access among sex workers over a 7-year period., Methods: Data were derived from An Evaluation of Sex Workers Health Access (AESHA), a community-based open prospective cohort of women (cis and trans) sex workers in Metro Vancouver, from 2014 to 2021. Descriptive statistics were used to summarize the proportion of primary care use in the past six months and to assess primary care trends over time from 2014-2021. We used multivariate logistic regression with generalized estimating equations (GEE) to identify structural factors associated with primary care access (seeing a family doctor in the last six months), after adjusting for confounders., Results: Amongst 646 participants, most (87.4%) accessed primary care at some point during the study period, and primary care use in the in the last 6 months was relatively stable (ranging from 60-78%) across each follow-up period. At first available observation, participants faced a high burden of sexually transmitted and blood-borne infections (STBBIs) (48.0%, 11.5%, and 10.4% were HCV, HIV, or STI seropositive, respectively), 56.8% were diagnosed with a mental health disorder, 8.1% had recently overdosed, and 14.7% were recently hospitalized. In multivariable GEE analysis, exposure to intimate partner violence was associated with reduced access to primary care (Adjusted odds ratios (AOR) 0.63, 95% Confidence interval (CI): 0.49 - 0.82), and limited English fluency was marginally associated (AOR 0.76 CI: 0.51 - 1.14)., Conclusions: This study characterized primary care access and its structural determinants among sex workers over 7-years. Participants faced a high burden of STBBIs and other health disparities, and a proportion faced gaps in primary care access. Scale-up of trauma-informed, culturally and linguistically tailored, sex worker-friendly primary care models are needed, alongside structural interventions to decriminalize and destigmatize sex work and substance use., Competing Interests: Competing interests: The authors declare that they have no competing interests.

The challenge of synthesizing noble metal nanostructures sustainably has encouraged researchers to explore biological routes for nanostructure production, such as biotemplating. Plant viruses with rod-shape morphology, such as tobacco mosaic virus (TMV) and barley stripe mosaic virus (BSMV), offer promising biotemplates to produce metal nanorods. TMV and BSMV can be incubated in aqueous metal precursor solutions to mineralize metals on the coat proteins (CPs) of the viruses. Previous studies have primarily examined palladium (Pd) mineralization on TMV and BSMV using Na 2 PdCl 4 as the Pd precursor. There is limited scientific literature on the effect of using alternative Pd precursor solutions besides Na 2 PdCl 4 such as K 2 PdCl 4 and PdCl 2 to mineralize Pd on TMV and BSMV. Past attempts at mineralizing other noble metals such as platinum (Pt) and gold (Au) required an initial layer of Pd to be deposited on the TMV and BSMV biotemplates. In this study, we aimed to expand the understanding of using alternative Pd precursor solutions to mineralize Pd on TMV and BSMV. Additionally, the deposition of Pt and Au onto TMV and BSMV without the need for an initial Pd mineralization layer was achieved using alternative Pt and Au precursors, including K 2 PtCl 4 and AuCl 3 , respectively. Pd, Pt, and Au were successfully deposited on TMV and BSMV by incubation in aqueous solutions of Na 2 PdCl 4 , K 2 PdCl 4 , PdCl 2 , K 2 PtCl 4 , and AuCl 3 . Kinetic studies were also conducted using ultraviolet-visible (UV-vis) spectroscopy to examine the rates at which Pd, Pt, and Au precursor ions were reduced during the mineralization process, mimicking their adsorption onto TMV and BSMV CPs. BSMV adsorbed noble metal precursor ions faster than TMV as determined by UV-vis spectroscopy. While palladium nanorods (PdNRs) offer high electrical conductivity desirable for electronic applications, Pd-coated TMV and BSMV may face limitations due to their organic cores, potentially compromising conductivity. To address this, one approach is to convert the organic core into conductive amorphous carbon through thermal annealing. In this study, in situ transmission electron microscopy was utilized to thermally anneal Pd-TMV2Cys, thereby transforming them into PdNRs with amorphous carbon cores., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The integration of smart technologies, including wearables and voice-activated devices, is increasingly recognized for enhancing the independence and well-being of older adults. However, the long-term dynamics of their use and the coadaptation process with older adults remain poorly understood. This scoping review explores how interactions between older adults and smart technologies evolve over time to improve both user experience and technology utility., Objective: This review synthesizes existing research on the coadaptation between older adults and smart technologies, focusing on longitudinal changes in use patterns, the effectiveness of technological adaptations, and the implications for future technology development and deployment to improve user experiences., Methods: Following the Joanna Briggs Institute Reviewer's Manual and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, this scoping review examined peer-reviewed papers from databases including Ovid MEDLINE, Ovid Embase, PEDro, Ovid PsycINFO, and EBSCO CINAHL from the year 2000 to August 28, 2023, and included forward and backward searches. The search was updated on March 1, 2024. Empirical studies were included if they involved (1) individuals aged 55 years or older living independently and (2) focused on interactions and adaptations between older adults and wearables and voice-activated virtual assistants in interventions for a minimum period of 8 weeks. Data extraction was informed by the selection and optimization with compensation framework and the sex- and gender-based analysis plus theoretical framework and used a directed content analysis approach., Results: The search yielded 16,143 papers. Following title and abstract screening and a full-text review, 5 papers met the inclusion criteria. Study populations were mostly female participants and aged 73-83 years from the United States and engaged with voice-activated virtual assistants accessed through smart speakers and wearables. Users frequently used simple commands related to music and weather, integrating devices into daily routines. However, communication barriers often led to frustration due to devices' inability to recognize cues or provide personalized responses. The findings suggest that while older adults can integrate smart technologies into their lives, a lack of customization and user-friendly interfaces hinder long-term adoption and satisfaction. The studies highlight the need for technology to be further developed so they can better meet this demographic's evolving needs and call for research addressing small sample sizes and limited diversity., Conclusions: Our findings highlight a critical need for continued research into the dynamic and reciprocal relationship between smart technologies and older adults over time. Future studies should focus on more diverse populations and extend monitoring periods to provide deeper insights into the coadaptation process. Insights gained from this review are vital for informing the development of more intuitive, user-centric smart technology solutions to better support the aging population in maintaining independence and enhancing their quality of life., International Registered Report Identifier (irrid): RR2-10.2196/51129., (©Kristina Marie Kokorelias, Alisa Grigorovich, Maurita T Harris, Umair Rehman, Louise Ritchie, AnneMarie M Levy, Kerstin Denecke, Josephine McMurray. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.08.2024.)

Aging in place (AIP) has emerged as a critical priority in policy to support older adults living in their homes and communities. However, achieving equitable support for older adults demands a multi-faceted approach that embraces their choices, capabilities and lived experiences while considering that place is a dynamic concept. This commentary explores the challenges older adults may encounter while AIP and identifies technological and policy areas to explore. Drawing insights from the UK, policy makers in Canada are urged to adopt inclusive definitions of AIP, prioritize technological solutions for recognized challenges and actively involve older adults in policy development., (Copyright © 2024 Longwoods Publishing.)

Background: Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings., Methods: Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum., Results: The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure., Conclusion: WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD., (© 2024. The Author(s).)

Cells activate stress response pathways to survive adverse conditions. Such responses involve the inhibition of global cap-dependent translation. This inhibition is a block that essential transcripts must escape via alternative methods of translation initiation, e.g., an internal ribosome entry site (IRES). IRESs have distinct structures and generally require a limited repertoire of translation factors. Cellular IRESs have been identified in many critical cellular stress response transcripts. We previously identified cellular IRESs in the murine insulin receptor (Insr) and insulin-like growth factor 1 receptor (Igf1r) transcripts and demonstrated their resistance to eukaryotic initiation factor 4F (eIF4F) inhibition. Here, we find that eIF5B preferentially promotes Insr, Igf1r, and hepatitis C virus IRES activity through a non-canonical mechanism that requires its highly charged and disordered N terminus. We find that the N-terminal region of eIF5B can drive cytoplasmic granule formation. This eIF5B granule is triggered by cellular stress and is sufficient to specifically promote IRES activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Germline pathogenic variants in the DNA mismatch repair (MMR) genes (Lynch syndrome) predispose to colorectal (CRC) and endometrial (EC) cancer. Lynch syndrome specific tumor features were evaluated for their ability to support the ACMG/InSiGHT framework in classifying variants of uncertain clinical significance (VUS) in the MMR genes. Twenty-eight CRC or EC tumors from 25 VUS carriers (6x MLH1 , 9x MSH2 , 6x MSH6 , 4x PMS2 ), underwent targeted tumor sequencing for the presence of microsatellite instability/MMR-deficiency (MSI-H/dMMR) status and identification of a somatic MMR mutation (second hit). Immunohistochemical testing for the presence of dMMR crypts/glands in normal tissue was also performed. The ACMG/InSiGHT framework reclassified 7/25 (28%) VUS to likely pathogenic (LP), three (12%) to benign/likely benign, and 15 (60%) VUS remained unchanged. For the seven re-classified LP variants comprising nine tumors, tumor sequencing confirmed MSI-H/dMMR (8/9, 88.9%) and a second hit (7/9, 77.8%). Of these LP reclassified variants where normal tissue was available, the presence of a dMMR crypt/gland was found in 2/4 (50%). Furthermore, a dMMR endometrial gland in a carrier of an MSH2 exon 1-6 duplication provides further support for an upgrade of this VUS to LP. Our study confirmed that identifying these Lynch syndrome features can improve MMR variant classification, enabling optimal clinical care.

Background: The Internet of Things (IoT) has gained significant attention due to advancements in technology and has potential applications in meeting the needs of an aging population. Smart technologies, a subset of IoT, can support older adults in aging in place, promoting independent living and improving their quality of life. However, there is a lack of research on how older adults and smart technologies coadapt over time to maximize their benefits and sustain adoption., Objective: We will aim to comprehensively review and analyze the existing scientific literature pertaining to the coadaptation between smart technologies and older adults. The primary focus will be to investigate the extent and nature of this coadaptation process and explore how older adults and technology coevolve over time to enhance older adults' experience with technology., Methods: This scoping review will follow the methodology outlined in the Joanna Briggs Institute Reviewer's Manual and adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews) guidelines for reporting. Peer-reviewed articles will be searched in databases like Ovid MEDLINE, OVID Embase, PEDro, OVID PsycINFO, EBSCO CINAHL, the Cochrane Library, Scopus, IEEE Xplore, Web of Science, and Global Index Medicus. The research team will create a data extraction form covering study characteristics, participant characteristics, underlying models and frameworks, research findings, implications for technology coadaptation, and any identified study limitations. A directed content analysis approach will be used, incorporating the Selection, Optimization, and Compensation framework and Sex- and Gender-Based Analysis Plus theoretical framework., Results: The results of this study are expected in January 2024., Conclusions: This scoping review endeavors to present a thorough overview of the available evidence concerning how smart technologies interact with older adults over an extended period. The insights gained from this review will lay the groundwork for a research program that explores how older adults adapt to and use smart technologies throughout their lives, ultimately leading to improved user satisfaction and experience and facilitating aging in place with tailored support and user-centered design principles., International Registered Report Identifier (irrid): PRR1-10.2196/51129., (©Kristina Marie Kokorelias, Alisa Grigorovich, Maurita T Harris, Umair Rehman, Louise Ritchie, AnneMarie Levy, Kerstin Denecke, Josephine McMurray. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.10.2023.)

Viruses and virus-like particles are powerful templates for materials synthesis because of their capacity for precise protein engineering and diverse surface functionalization. We recently developed a recombinant bacterial expression system for the production of barley stripe mosaic virus-like particles (BSMV VLPs). However, the applicability of this biotemplate was limited by low stability in alkaline conditions and a lack of chemical handles for ligand attachment. Here, we identify and validate novel residues in the BSMV Caspar carboxylate clusters that mediate virion disassembly through repulsive interactions at high pH. Point mutations of these residues to create attractive interactions that increase rod length ~2 fold, with an average rod length of 91 nm under alkaline conditions. To enable diverse chemical surface functionalization, we also introduce reactive lysine residues at the C-terminus of BSMV coat protein, which is presented on the VLP surface. Chemical conjugation reactions with this lysine proceed more quickly under alkaline conditions. Thus, our alkaline-stable VLP mutants are more suitable for rapid surface functionalization of long nanorods. This work validates novel residues involved in BSMV VLP assembly and demonstrates the feasibility of chemical functionalization of BSMV VLPs for the first time, enabling novel biomedical and chemical applications.

Background: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer., Methods: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken., Results: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing., Conclusions: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. In total, 86.9% of the 137 SLS tumors could be resolved into established subtypes. For 22.6% of these resolved SLS cases, primary MLH1 epimutations (2.2%) as well as previously undetected germline MMR pathogenic variants (1.5%), tumor MLH1 methylation (13.1%) or false positive dMMR IHC (5.8%) results were identified. Double somatic MMR gene mutations were the major cause of dMMR identified across each tumor type (73.9% of resolved cases, 64.2% overall, 70% of CRC, 45.5% of ECs and 70.8% of SSTs). The unresolved SLS tumors (13.1%) comprised tumors with only a single somatic (7.3%) or no somatic (5.8%) MMR gene mutations. A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations., (© 2023. The Author(s).)

Older adults with a chronic health condition (e.g., hypertension) use various self-management methods. Healthcare technologies have the potential to support health self-management. However, it is necessary to understand the acceptance of these technologies as a precursor to older adults' adoption and integration into their health plan. Our focus was on the factors older adults with hypertension initially consider when introduced to three new healthcare technologies that might support their health self-management. We compared their considerations for a blood pressure monitor, an electronic pillbox, and a multifunction robot to simulate incrementally more complex technologies. Twenty-three participants (aged 65-84) completed four questionnaires and a semi-structured interview. The interview transcripts were analyzed using a thematic analysis approach. We identified the factors that were frequently mentioned among the participants for each of the three healthcare technologies. The factors that older adults initially considered were familiarity, perceived benefits, perceived ease of use, perceived need for oneself, relative advantage, complexity, and perceived need for others. Upon further reflection, participants considered advice acceptance, compatibility, convenience, facilitating conditions, perceived usefulness, privacy, subjective norm, and trust. We integrated the factors that older adults considered into the Healthcare Technology Acceptance Model (H-TAM), which elucidates the complexity of healthcare technology acceptance and provides guidance for future explorations., Competing Interests: Statement of conflict of interest: The authors declare no conflicts of interest.

Background: Women who use drugs (WWUD) and engage in sex work experience disproportionate sex- and drug-related harms, such as HIV, however comparatively little is known about their overdose risk. Therefore, we examined the association between sex work and overdose and secondarily explored the association of social-structural factors, such as policing and gendered violence, with overdose., Methods: Data were derived from two community cohort studies based in Vancouver, Canada between 2005 to 2018. We used logistic regression with GEE to examine the associations between a) sex work and nonfatal overdose and b) social-structural and individual variables with overdose among WWUD who engaged in sex work during the study. Sex work, overdose, and other variables were time-updated, captured every six months., Results: Among 857 WWUD included, 56% engaged in sex work during the study. Forty-three percent of WWUD engaged in sex work had at least one overdose compared to 26% of WWUD who did not. Sex work was not significantly associated with an increased odds of overdose (AOR = 1.14, 95% CI: 0.93-1.40). In the exploratory analysis amongst 476 WWUD engaged in sex work, social-structural variables associated with overdose in the multivariable model included exposure to: punitive policing (OR = 1.97, 95% CI: 1.30-2.96) and physical or sexual violence (OR = 2.55, 95% CI: 1.88-3.46)., Conclusions: WWUD engaged in sex work had an increased overdose burden that may be driven by social-structural factors rather than sex work itself. Interventions that address policing and gendered violence represent potential targets for effective overdose prevention., Competing Interests: Declarations of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

IRES mediated translation initiation requires a different repertoire of factors than canonical cap-dependent translation. Treatments that inhibit the canonical translation factor EIF4G1 have little or no effect on the ability of the Insr and Igf1r cellular IRESes to promote translation. Transcripts for two cellular receptors contain RNA elements that facilitate translation initiation without intact EIF4G1. Cellular IRES mechanisms may resemble viral type III IRESes allowing them to promote translate with a limited number of initiation factors allowing them to work under stress conditions when canonical translation is repressed.

Background: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 ( 32 P) microparticles, combined with standard-of-care chemotherapy., Patients and Methods: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32 P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks., Results: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32 P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32 P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively., Conclusions: Endoscopic ultrasound-guided 32 P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32 P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC., Competing Interests: Disclosure PJR: stock and other ownership interests: Perci Health Ltd. Honoraria: Sirtex Medical, Eisai, Servier, Pierre Fabre, Shire, Roche, AstraZeneca, Merck. Consulting or advisory role: Sirtex Medical, Eisai, Servier, Roche, AstraZeneca, Amgen. Speakers’ bureau: Amgen, Merck, Servier, Boston Scientific. Research funding: Sanofi, Bayer. Travel, accommodations, expenses: Roche, Ipsen. HSW: honoraria: BTG/Biocompatibles, Merck KGaA, and BMS. Consulting or advisory role: Incyte, Bayer, Roche/Genentech/ Foundation Medicine, Sirtex Medical, Celgene, OncoSil Medical, and Zymeworks. Research funding: Pfizer, Sirtex and Zymeworks. Travel, accommodations, expenses: BTG/Biocompatibles, Merck KGaA, and BMS. DC: stock and other ownership interests: MarginClear. Consulting or advisory role: Boston Scientific and OncoSil Medical. Research funding: Boston Scientific. MN: stock and other ownership interests: Pakinax Pty Ltd and Margin Clear Pty Ltd. DB: employment: SA Medical Imaging and SA Health. Research funding: Avener/Pankind and AstraZeneca. NEW: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. DMT: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. DCJ: employment: OncoSil Medical Ltd. Stock and other ownership interests: OncoSil Medical Ltd. EY: employment: Southern Star Research Pty Ltd (contractor to OncoSil Medical Ltd). All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In water, the surfactant dioctyl sulfosuccinate (Aerosol-OT or AOT) exhibits diverse aggregate structures, ranging from micelles to lamella. An atomic-level understanding, however, of the formation and structure of these aggregates is lacking. Herein, using atomistic molecular dynamics (MD) with microsecond-long simulations, self-assembly of AOT in water is studied for concentrations of 1, 7.2, and 20 wt % at 293 K and for 7.2 wt % at 353 K. Assembly proceeds through stepwise association and dissociation of single AOT molecules, and the fusion and fission of AOT clusters. At 293 K, AOT self-assembles into either (i) spherical micelles (1 wt %), (ii) biphasic systems consisting of rod-like and prolate spheroidal micelles (7.2 wt %), or (iii) bilayers (20 wt %). We hypothesize that the observed rod-like structure is a precursor to lamellar microdomains found experimentally in biphasic dispersions. Increasing temperature to 353 K at 7.2 wt % results in a system consisting of prolate micelles but no rod-like micelles. Simulated phase behavior agrees with previously published experimental observations. Individual aggregates formed during self-assembly are identified using graph theory. Structural metrics of these aggregates like the radius of gyration, shape anisotropy, and prolateness are presented. Trends in structural metrics quantitatively reflect how shapes and sizes of AOT aggregates vary with surfactant concentration and temperature. These simulations provide deeper insight into open questions in the scientific community and demonstrate a method to generate physics-based micelle structures that can be used to rationalize experimental observations.

Background: The Ottawa Inner City Health's Managed Opioid Program is the first, to our knowledge, to pair injectable opioid agonist hydromorphone treatment with assisted housing for people experiencing homelessness with severe opioid use disorder (OUD) and injection drug use. We aimed to describe this program and evaluate retention, health, and social wellbeing outcomes., Methods: We retrospectively assessed the first cohort of clients enrolled in the Managed Opioid Program between August 2017-2018. The primary outcome was retention at 12 months. Secondary outcomes included injectable and oral opioid dose titration, non-prescribed opioid use, overdoses, connection with behavioural health services, and social well-being. Descriptive statistics were used to summarize baseline demographics and secondary outcomes. Actuarial survival analysis was used to assess retention among participants., Results: The study sample included 26 participants: median age was 36 years, 14 were female, 22 were White, eight had alcohol use disorders, 25 had stimulant use disorders, and all had a history of concurrent psychiatric illness. Retention at 12 months was 77% (95% CI 62-95). Throughout the first-year participants' opioid treatment doses increased. The median daily dose of injectable hydromorphone was 36 mg [17-54 mg] and 156 mg [108-188 mg] at enrollment and one year respectively. The median daily dose of oral opioid treatment was 120-milligram morphine equivalents [83-180 mg morphine equivalents] and 330-milligram morphine equivalents [285-428 mg morphine equivalents] at enrollment and one year respectively. Over half had no overdoses and there were no deaths among participants who remained enrolled. At one year, 45% stopped non-prescribed opioid use, 96% connected to behavioral health services, 73% reconnected with estranged families, and 31% started work or vocational programs., Conclusion: Individuals with severe OUD engaged in injectable hydromorphone treatment and housing showed high retention in care and substantive improvements in patient-centered health and social well-being outcomes., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In the United States, the criminalization and stigmatization of drug use and sex work contribute to infectious disease transmission and healthcare disengagement. People who inject drugs (PWID) and engage in sex work experience exacerbated HIV risk. In the context of the ongoing HIV and overdose epidemics little research describes why PWID engage in sex work and its relative HIV risk. To inform intervention needs, we aimed to create a typology of sex work among PWID with a focus on HIV risk and healthcare utilization behaviours., Methods: We drew from in-depth interviews conducted across Massachusetts and Rhode Island from 2016-2019. Participants were ≥18 years old and self-reported past-month injection drug use and HIV-negative status. Using data from individuals reporting sex work experience (n=33/78), we utilized the framework method to develop a typology of perspectives on sex work engagement and attributes pertaining to HIV risk and healthcare utilization behaviours., Results: We uncovered varying perspectives on sex work and associated HIV risks and prevention needs. A typology included three groups who viewed their sex work engagement as a (1) consistent job, (2) income supplement, or (3) survival method to abate withdrawal symptoms. The first group described more consistent sexual and injection behaviours to mitigate HIV risk than the second group. The third group appeared particularly vulnerable to HIV, describing inconsistent condom use and frequent sharing of injection equipment, low healthcare utilization, and limited disclosure of sex work and injection drug use to healthcare providers., Conclusion: Findings highlight distinct perspectives on sex work among PWID involved in it and corresponding perceptions of HIV risk and healthcare utilization behaviours. Understanding the nuances in sex work engagement among PWID can inform interventions to prevent infectious disease transmission, including efforts to further connect this marginalized population to harm reduction, health, and low barrier opioid treatment services., Competing Interests: Declarations of Interest No conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Distress tolerance has fuzzy boundaries with neighboring emotion regulation abilities. In the present study, we probed the structure of this domain and examined its link to emotional disorder outcomes. We recruited mental health patient ( n s = 225 and 210) and university student ( n = 1,525) samples to report on diverse components of distress tolerance, emotion dysregulation, experiential avoidance, and anxiety sensitivity. Confirmatory factor analysis supported a one-factor model of these individual differences; this broad dimension was closely related to depressive symptoms (standardized effect range = .63 to .74) and suicide risk (.42 to .50), and it was almost perfectly associated with a latent dimension representing borderline personality disorder features (.93-.97). We conclude that a reformulation of this domain-with special attention to discriminant validity-would help understand how distress tolerance is so intimately intertwined with emotional health. The data sets and analysis code for this study are published at https://osf.io/8ab2v/.

Biomolecules are increasingly attractive templates for the synthesis of functional nanomaterials. Chief among them is the plant tobacco mosaic virus (TMV) due to its high aspect ratio, narrow size distribution, diverse biochemical functionalities presented on the surface, and compatibility with a number of chemical conjugations. These properties are also easily manipulated by genetic modification to enable the synthesis of a range of metallic and non-metallic nanomaterials for diverse applications. This article reviews the characteristics of TMV and related viruses, and their virus-like particle (VLP) derivatives, and how these may be manipulated to extend their use and function. A focus of recent efforts has been on greater understanding and control of the self-assembly processes that drive biotemplate formation. How these features have been exploited in engineering applications such as, sensing, catalysis, and energy storage are briefly outlined. While control of VLP surface features is well-established, fewer tools exist to control VLP self-assembly, which limits efforts to control template uniformity and synthesis of certain templated nanomaterials. However, emerging advances in synthetic biology, machine learning, and other fields promise to accelerate efforts to control template uniformity and nanomaterial synthesis enabling more widescale industrial use of VLP-based biotemplates., (© 2020 Wiley-VCH GmbH.)

Objective: The purpose of this study is to identify subgroups of people with schizophrenia on the basis of self-assessment accuracy (metacognition) and examine group differences in rehabilitation potential., Method: Participants were 51 individuals with schizophrenia-spectrum disorders recruited from community mental health centers. Data from a self-report measure of cognition and a neuropsychological battery were compared and utilized to place participants in 3 accuracy groups: overestimators, accurate estimators, and underestimators. A multivariate analysis of variance was used to compare performance between accuracy groups on an index of rehabilitation potential., Results: Three distinct profiles of metacognitive ability were identified. The analysis found that participants who underestimated their cognitive functioning had the highest scores on an index of rehabilitation potential (learning potential), and those who overestimated their functioning had the lowest. No significant differences in diagnostic or sociodemographic variables were found among accuracy groups., Conclusions and Implications for Practice: Results suggest that there are differences in the way people with schizophrenia evaluate their cognition and, further, these metacognitive profiles are associated with differences in the ability to learn new tasks quickly. Thus, identifying subgroups of individuals based on metacognitive processing may help identify those most likely to benefit from cognitive remediation and other rehabilitative therapies. Future research should explore the link between metacognitive ability and rehabilitation potential in greater detail. Future investigations should also clarify the implications that underestimation of ability has for overall recovery and quality of life in people with schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Vibrio natriegens , a fast-growing Gram-negative bacterium, is gaining interest as a platform for rapid biotechnology applications and metabolic engineering. Only a few bacteriophages that infect this bacterium have been identified. Here, we describe the isolation and characterization of two V. natriegens bacteriophages isolated from Hatches Creek, Wellfleet, Massachusetts., (Copyright © 2020 Harris et al.)

Aging in place (AIP) is a term that is commonly used and defined in a plethora of ways. Multiple disciplines take a different stance on the definition of AIP, and its definition has evolved over time. Such diverse ways to define AIP could be a barrier to reach a shared expectation among multiple stakeholders when formulating research studies, making policy decisions, developing care plans, or designing technology tools to support older adults. We conducted a scoping review for the term AIP to understand specifically how it has been defined across time and disciplines. We collected exemplary definitions of AIP from 7 databases that represent different fields of study; namely, AgeLine, Anthropology Plus, Art and Architecture Source, CINAHL, PsycINFO, PubMed, and SocINDEX. We conducted a thematic analysis to identify the common concepts that emerged across the definitions identified in the scoping review. We developed 3 main categories from the themes: space, person, and time to illustrate the root of meaning across the definitions. Intersectionality across the categories yielded a comprehensive understanding of AIP, which does not constrain its definition to a place-related phenomenon. We propose that AIP be defined as " One's journey to maintain independence in one's place of residence as well as to participate in one's community ." With this shared understanding of the term AIP, policymakers, researchers, technology designers, and caregivers can better support those who aim to age in the place of their choice., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy., Methods: Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/m 2 and gemcitabine 1000 mg/m 2 on days 1, 8, and 15 (28-day cycle) presurgery, and four cycles postoperatively. Early response to chemotherapy was measured with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans on day 15., Results: Preoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 (< 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months., Conclusions: The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a > 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies.

Toxoplasma gondii is a protozoan parasite that has a tremendous impact on human health and livestock. High seroprevalence among humans and other animals is facilitated by the conversion of rapidly proliferating tachyzoites into latent bradyzoites that are housed in tissue cysts, which allow transmission through predation. Epigenetic mechanisms contribute to the regulation of gene expression events that are crucial in both tachyzoites as well as their development into bradyzoites. Acetylation of histones is one of the critical histone modifications that is linked to active gene transcription. Unlike most early-branching eukaryotes, Toxoplasma possesses two GCN5 homologues, one of which, GCN5b, is essential for parasite viability. Surprisingly, GCN5b does not associate with most of the well-conserved proteins found in the GCN5 complexes of other eukaryotes. Of particular note is that GCN5b interacts with multiple putative transcription factors that have plant-like DNA-binding domains denoted as AP2. To understand the function of GCN5b and its role(s) in epigenetic gene regulation of stage switching, we performed co-immunoprecipitation of GCN5b under normal and bradyzoite induction conditions. We report the greatest resolution of the GCN5b complex to date under these various culture conditions. Moreover, reciprocal co-IPs were performed with distinct GCN5b-interacting AP2 factors (AP2IX-7 and AP2XII-4) to delineate the interactomes of each putative transcription factor. Our findings suggest that GCN5b is associated with at least two distinct complexes that are characterized by two different pairs of AP2 factors, and implicate up to four AP2 proteins to be involved with GCN5b-mediated gene regulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active capping state. Knockdowns of Twinfilin and CP each cause similar defects in cell morphology, and elevated Twinfilin expression rescues defects caused by CARMIL hyperactivity. Together, these observations define Twinfilin as the first 'pro-capping' ligand of CP and lead us to propose important revisions to our understanding of the CP regulatory cycle., Competing Interests: AJ, DH, PM, BJ, MH, AS, GA, JC, BG No competing interests declared, (© 2018, Johnston et al.)

The ABC transporter ABCG1 contributes to the regulation of cholesterol efflux from cells and to the distribution of cholesterol within cells. We showed previously that ABCG1 deficiency inhibits insulin secretion by pancreatic beta cells and, based on its immunolocalization to insulin granules, proposed its essential role in forming granule membranes that are enriched in cholesterol. While we confirm elsewhere that ABCG1, alongside ABCA1 and oxysterol binding protein OSBP, supports insulin granule formation, the aim here is to clarify the localization of ABCG1 within insulin-secreting cells and to provide added insight regarding ABCG1's trafficking and sites of function. We show that stably expressed GFP-tagged ABCG1 closely mimics the distribution of endogenous ABCG1 in pancreatic INS1 cells and accumulates in the trans-Golgi network (TGN), endosomal recycling compartment (ERC) and on the cell surface but not on insulin granules, early or late endosomes. Notably, ABCG1 is short-lived, and proteasomal and lysosomal inhibitors both decrease its degradation. Following blockade of protein synthesis, GFP-tagged ABCG1 first disappears from the ER and TGN and later from the ERC and plasma membrane. In addition to aiding granule formation, our findings raise the prospect that ABCG1 may act beyond the TGN to regulate activities involving the endocytic pathway, especially as the amount of transferrin receptor is increased in ABCG1-deficient cells. Thus, ABCG1 may function at multiple intracellular sites and the plasma membrane as a roving sensor and modulator of cholesterol distribution, membrane trafficking and cholesterol efflux., Competing Interests: The authors have declared that no competing interests exist

Capillary flow and Marangoni flow influence flow patterns of an evaporating liquid drop. While it is obvious that Marangoni stress on the drop surface affects the surface flow direction, we found that capillary flow also has an impact. The numerical results of this study showed a stagnation point near the contact line, which was further explained by the lubrication theory. The stagnation point is produced by the competing effects of Marangoni flow and capillary flow and emerges when the contact angle is small because the divergence of the capillary flow near the contact line increases as the contact angle decreases. The radial position of the stagnation point from the numerical results ( r numerical ≈ 0.995) agreed with the experimentally observed stagnation point ( r experimental > 0.992).

In pancreatic β-cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood. ATP binding cassette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion. RNAi inter-ference-induced depletion in cultured pancreatic β-cells shows that ABCG1 is needed to stabilize newly made insulin granules against lysosomal degradation; ABCA1 is also involved but to a lesser extent. Both transporters are also required for optimum glucose-stimulated insulin secretion, likely via complementary roles. Exogenous cholesterol addition rescues knockdown-induced granule loss (ABCG1) and reduced secretion (both transporters). Another cholesterol transport protein, oxysterol binding protein (OSBP), appears to act proximally as a source of endogenous cholesterol for granule formation. Its knockdown caused similar defective stability of young granules and glucose-stimulated insulin secretion, neither of which were rescued with exogenous cholesterol. Dual knockdowns of OSBP and ABC transporters support their serial function in supplying and concentrating cholesterol for granule formation. OSBP knockdown also decreased proinsulin synthesis consistent with a proximal endoplasmic reticulum defect. Thus, membrane cholesterol distribution contributes to insulin homeostasis at production, packaging, and export levels through the actions of OSBP and ABCs G1 and A1.

Kinetoplastid-based infections are neglected diseases that represent a significant human health issue. Chemotherapeutic options are limited due to toxicity, parasite susceptibility, and poor patient compliance. In response, we studied a molecular-target-directed approach involving intervention of hexokinase activity-a pivotal enzyme in parasite metabolism. A benzamidobenzoic acid hit with modest biochemical inhibition of Trypanosoma brucei hexokinase 1 (TbHK1, IC 50 =9.1 μm), low mammalian cytotoxicity (IMR90 cells, EC 50 >25 μm), and no appreciable activity on whole bloodstream-form (BSF) parasites was optimized to afford a probe with improved TbHK1 potency and, significantly, efficacy against whole BSF parasites (TbHK1, IC 50 =0.28 μm; BSF, ED 50 =1.9 μm). Compounds in this series also inhibited the hexokinase enzyme from Leishmania major (LmHK1), albeit with less potency than toward TbHK1, suggesting that inhibition of the glycolytic pathway may be a promising opportunity to target multiple disease-causing trypanosomatid protozoa., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The vast unexplored virus biodiversity makes the application of virus templates to nanomaterial synthesis especially promising. Here, a new biotemplate, Barley stripe mosaic virus (BSMV) was successfully used to synthesize organic-metal nanorods of similarly high quality to those produced with Tobacco mosaic virus (TMV). The mineralization behavior was characterized in terms of the reduction and adsorption of precursor and nanocrystal formation processes. The BSMV surface-mediated reduction of Pd (2+) proceeded via first-order kinetics in both Pd (2+) and BSMV. The adsorption equilibrium relationship of PdCl 3 H 2 O - on the BSMV surface was described by a multistep Langmuir isotherm suggesting alternative adsorbate-adsorbent interactions when compared to those on TMV. It was deduced that the first local isotherm is governed by electrostatically driven adsorption, which is then followed by sorption driven by covalent affinity of metal precursor molecules for amino acid residues. Furthermore, the total adsorption capacity of palladium species on BSMV is more than double of that on TMV. Finally, study of the BSMV-Pd particles by combining USAXS and SAXS enabled the characterization of all length scales in the synthesized nanomaterials. Results confirm the presence of core-shell cylindrical particles with 1-2 nm grains. The nanorods were uniform and monodisperse, with controllable diameters and therefore, of similar quality to those synthesized with TMV. Overall, BSMV has been confirmed as a viable alternate biotemplate with unique biomineralization behavior. With these results, the biotemplate toolbox has been expanded for the synthesis of new materials and comparative study of biomineralization processes.

There is a lack of fundamental information about the molecular processes governing biomineralization of inorganic materials to produce nanostructures on biological templates. This information is essential for the directed synthesis of high quality nanomaterials via biotemplating. We characterized palladium (Pd) mineralization via the individual adsorption, reduction, and nanocrystal growth processes, which simultaneously occur during the hydrothermal synthesis on the Tobacco mosaic virus (TMV). The adsorption of precursor and reduction of palladium were decoupled through UV-vis Spectroscopy and in situ X-ray absorption spectroscopy studies. The role of additional cysteine (Cys) residues, ionic strength, and coating density on the fundamental parameters describing these processes were quantitatively evaluated. Primary nanocrystal growth and structural orientation of Pd nanoparticles was characterized using in situ small angle X-ray scattering. The adsorption, reduction of Pd species, and nanocrystal sizes were significantly changed on addition of Cys residues to the amino terminus of the TMV coat protein. Reduction of Pd on an already coated virion was dependent on the Pd surface area, and was hindered by the presence of residual salt. Furthermore, trends in Pd adsorption intensity and capacity suggested that chloride ions affected the adsorption equilibrium. Application of this fundamental approach with further optimization of parameters dictating biomineralization would facilitate directed synthesis and scale up of bioinorganic systems., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Infectious disease (ID) consultations have been shown to increase adherence to guidelines and decrease mortality for patients with Staphylococcus aureus bacteremia (SAB). Here, we assessed the impact of a mandatory ID consultation policy for SAB., Methods: We retrospectively reviewed all consecutive adult patients with SAB at two tertiary care teaching hospitals in Hamilton, ON, Canada. Mandatory ID consults for SAB were implemented on January 1(st) 2012. We compared SAB cases in 2011 (control group) with those in 2012 (intervention group). Outcomes included adherence to the Infectious Diseases Society of America guidelines and patient outcomes., Results: We reviewed 128 SAB cases in 2011 and 124 in 2012. The majority of S. aureus were methicillin-susceptible (97/128, 75.8 % in 2011 and 100/124, 80.6 % in 2012). ID involvement increased significantly from 93/128 (72.7 %) in 2011, to 103/124 (83.1 %) in 2012 (odds ratio [OR] 1.9, 95 % confidence interval [CI] 1.1-3.3, p = 0.047). There was also a significant decrease in the median time to ID involvement from 2 days to 1 (p = 0.001). In patients who survived the minimum treatment course (greater than 13 days), there was a significant improvement in adherence to IDSA guidelines in 2012 (65/102, 63.7 % vs. 77/96, 80.2 %; OR 2.3, 95 % CI 1.2-4.4, p = 0.01). Mortality and SAB relapse rates were similar in both groups., Conclusions: Creating an automated ID consultation for SAB led to an increase in involvement of ID, a significant decrease in time to ID involvement, and better adherence to IDSA guidelines. The study was not sufficiently powered to detect significant changes in mortality and SAB relapse rates.

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.